TGFR2_HUMAN » TGF-beta receptor type-2

TGFR2_HUMAN » TGF-beta receptor type-2
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Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
TGFR2_HUMAN » TGF-beta receptor type-2 » TGFR-2; TGF-beta type II receptor;Transforming growth factor-beta receptor type II;TGF-beta receptor type II; TbetaR-II;
Hydrophobic Thickness 41.2 ± 4.6 Å
Tilt Angle 18 ± 11°
ΔGtransfer -29.7 kcal/mol
ΔGfold -14.7 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, HMDB
Topology Out
TM Segments 160-189 (158-195)
Pathways

Adherens junction (KEGG)

Chagas disease (KEGG)

Chronic myeloid leukemia (KEGG)

Colorectal cancer (KEGG)

Cytokine-cytokine receptor interaction (KEGG)

Endocytosis (KEGG)

Hippo signaling pathway (KEGG)

HTLV-I infection (KEGG)

MAPK signaling pathway (KEGG)

Osteoclast differentiation (KEGG)

Pancreatic cancer (KEGG)

Pathways in cancer (KEGG)

Signal Transduction (Reactome)

TGF-beta signaling pathway (KEGG)

Transcriptional misregulation in cancer (KEGG)

PDB 1plo (38-159), 1m9z (49-159), 1ktz (B=38-159), 2pjy (B=42-149), 3kfd (E/F/G/H=38-153)
OPM none
Complexes

TGFB3:TGFR1:TGFR2_HUMAN

TGFR1:TGFR2:TGFB1_HUMAN

Interactions

A4, Complex: TGFR2:A4, PubMed

ACVL1, Complex: ACVL1:TGFR2, PubMed

ACVR1, Complex: TGFR2:ACVR1, PubMed

CD44, Complex: CD44:TGFR2, PubMed

EGLN, Complex: TGFR2:EGLN, PubMed

NRP1, Complex: TGFR2:NRP1

NRP2, Complex: TGFR2:NRP2

PGFRA, Complex: PGFRA:TGFR2, PubMed

TGBR3, Complex: TGBR3:TGFR2, PubMed

TGFR1, Complex: TGFB3:TGFR1:TGFR2, PDBID: 2pjy

Domains

AA: 49-159, PDBID: 1KTZ, Subunit B, Seq Identity:100%, Transforming growth factor beta receptor 2 ectodomain

AA: 244-538, PDBID: 3MY0, Subunit H, Seq Identity:41%, Protein tyrosine kinase

UniProt annotation for TGFR2_HUMAN » TGF-beta receptor type-2
FUNCTION: Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, the non- promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and the activation of TGFRB1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non- canonical, SMAD-independent TGF-beta signaling pathways.

CATALYTIC ACTIVITY: ATP + [receptor-protein] = ADP + [receptor- protein] phosphate.

SUBUNIT: Homodimer. Heterohexamer; TGFB1, TGFB2 and TGFB3 homodimeric ligands assemble a functional receptor composed of two TGFBR1 and TGFBR2 heterodimers to form a ligand-receptor heterohexamer. The respective affinity of TGFRB1 and TGFRB2 for the ligands may modulate the kinetics of assembly of the receptor and may explain the different biological activities of TGFB1, TGFB2 and TGFB3. Interacts with DAXX. Interacts with TCTEX1D4. Interacts with ZFYVE9; ZFYVE9 recruits SMAD2 and SMAD3 to the TGF- beta receptor. Interacts with and is activated by SCUBE3; this interaction does not affect TGFB1-binding to TGFBR2. Interacts with VPS39; this interaction is independent of the receptor kinase activity and of the presence of TGF-beta.

DISEASE: Hereditary non-polyposis colorectal cancer 6 (HNPCC6) OMIM: An autosomal dominant disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early-onset colorectal carcinoma (CRC) and extra-colonic tumors of the gastrointestinal, urological and female reproductive tracts. HNPCC is reported to be the most common form of inherited colorectal cancer in the Western world. Clinically, HNPCC is often divided into two subgroups. Type I is characterized by hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II is characterized by increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical HNPCC is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term "suspected HNPCC" or "incomplete HNPCC" can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected. mutations affecting the gene represented in this entry.

DISEASE: Esophageal cancer (ESCR) OMIM: A malignancy of the esophagus. The most common types are esophageal squamous cell carcinoma and adenocarcinoma. Cancer of the esophagus remains a devastating disease because it is usually not detected until it has progressed to an advanced incurable stage. mutations affecting the gene represented in this entry.

DISEASE: Loeys-Dietz syndrome 2 (LDS2) OMIM: An aortic aneurysm syndrome with widespread systemic involvement, characterized by arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate. Physical findings include prominent joint laxity, easy bruising, wide and atrophic scars, velvety and translucent skin with easily visible veins, spontaneous rupture of the spleen or bowel, and catastrophic complications of pregnancy, including rupture of the gravid uterus and the arteries, either during pregnancy or in the immediate postpartum period. Some patients have craniosynostosis, exotropy, micrognathia and retrognathia, structural brain abnormalities, and intellectual deficit. Note=The disease is caused by mutations affecting the gene represented in this entry. TGFBR2 mutations Cys-460 and His-460 have been reported to be associated with thoracic aortic aneurysms and dissection (TAAD). This phenotype, also known as thoracic aortic aneurysms type 3 (AAT3), is distinguised from LDS2 by having aneurysms restricted to thoracic aorta. As individuals carrying these mutations also exhibit descending aortic disease and aneurysms of other arteries (PubMed), they have been considered as LDS2 by the OMIM resource.

UniProt features for TGFR2_HUMAN » TGF-beta receptor type-2
SIGNAL 1 22
CHAIN 23 567 TGF-beta receptor type-2.
DOMAIN 244 544 Protein kinase.
ACT_SITE 379 379 Proton acceptor (By similarity).
DISULFID 51 84
DISULFID 54 71
DISULFID 61 67
DISULFID 77 101
DISULFID 121 136
DISULFID 138 143
Amino Acid Sequence for TGFR2_HUMAN » TGF-beta receptor type-2
MGRGLLRGLW PLHIVLWTRI ASTIPPHVQK SVNNDMIVTD NNGAVKFPQL CKFCDVRFST CDNQKSCMSN CSITSICEKP QEVCVAVWRK NDENITLETV CHDPKLPYHD FILEDAASPK CIMKEKKKPG ETFFMCSCSS DECNDNIIFS EEYNTSNPDL LLVIFQVTGI SLLPPLGVAI SVIIIFYCYR VNRQQKLSST WETGKTRKLM EFSEHCAIIL EDDRSDISST CANNINHNTE LLPIELDTLV GKGRFAEVYK AKLKQNTSEQ FETVAVKIFP YEEYASWKTE KDIFSDINLK HENILQFLTA EERKTELGKQ YWLITAFHAK GNLQEYLTRH VISWEDLRKL GSSLARGIAH LHSDHTPCGR PKMPIVHRDL KSSNILVKND LTCCLCDFGL SLRLDPTLSV DDLANSGQVG TARYMAPEVL ESRMNLENVE SFKQTDVYSM ALVLWEMTSR CNAVGEVKDY EPPFGSKVRE HPCVESMKDN VLRDRGRPEI PSFWLNHQGI QMVCETLTEC WDHDPEARLT AQCVAERFSE LEHLDRLSGR SCSEEKIPED GSLNTTK